Arrhythmias

• Arrhythmia is loss of cardiac rhythm, especially irregularity of heartbeat.

PATHOPHYSIOLOGY

SUPRAVENTRICULAR ARRHYTHMIAS

• Common supraventricular tachycardias requiring drug treatment are atrial fibrillation (AF), atrial flutter, and paroxysmal supraventricular tachycardia (PSVT). Other arrhythmias that usually do not require drug therapy are not discussed here (eg,) pemature atrial complexes, sinus arrhythmia, sinus tachycardia).

Atrial Fibrillation and Atrial Flutter

• AF has extremely rapid (400–600 atrial beats/min) and disorganized atrial activation. There is loss of atrial contraction (atrial kick), and supraventricular impulses penetrate the atrioventricular (AV) conduction system to variable degrees, resulting in irregular ventricular activation and irregularly irregular pulse (120–180 beats/min).

• Atrial flutter has rapid (270–330 atrial beats/min) but regular atrial activation. Ventricular response usually has a regular pattern and a pulse of 300 beats/min. This arrhythmia occurs less frequently than AF but has similar precipitating factors, consequences, and drug therapy.

• The predominant mechanism of AF and atrial flutter is reentry, which is usually associated with organic heart disease that causes atrial distention (eg, ischemia or infarction, hypertensive heart disease, and valvular disorders). Additional associated disorders include acute pulmonary embolus and chronic lung disease, resulting in pulmonary hypertension and cor pulmonale, and states of high adrenergic tone such as thyrotoxicosis, alcohol withdrawal, sepsis, and excessive physical exertion.

Paroxysmal Supraventricular Tachycardia Caused by Reentry

• PSVT arising by reentrant mechanisms includes arrhythmias caused by AV nodal reentry, AV reentry incorporating an anomalous AV pathway, sinoatrial (SA) nodal reentry, and intraatrial reentry.

VENTRICULAR ARRHYTHMIAS

Premature Ventricular Complexes

• Premature ventricular complexes (PVCs) can occur in patients with or without heart disease.

Ventricular Tachycardia

• Ventricular tachycardia (VT) is defined by three or more repetitive PVCs occurring at a rate greater than 100 beats/min. It is a wide QRS tachycardia that may result acutely from severe electrolyte abnormalities (hypokalemia or hypomagnesemia), hypoxia, drug toxicity (eg, digoxin), or (most commonly) during an acute myocardial infarction (MI) or ischemia complicated by heart failure (HF). The chronic recurrent form is almost always associated with organic heart disease (eg, idiopathic dilated cardiomyopathy or remote MI with left ventricular [LV] aneurysm).

• Sustained VT is that which requires intervention to restore a stable rhythm or persists a relatively long time (usually >30 s). Nonsustained VT self-terminates after a brief duration (usually <30 s). Incessant VT refers to VT occurring more frequently than sinus rhythm, so that VT becomes the dominant rhythm. Monomorphic VT has a consistent QRS configuration, whereas polymorphic VT has varying QRS complexes. Torsade de pointes (TdP) is a polymorphic VT in which the QRS complexes appear to undulate around a central axis.

Ventricular Proarrhythmia

• Proarrhythmia refers to the development of a significant new arrhythmia, such as VT, ventricular fibrillation (VF), or TdP, or worsening of an existing arrhythmia. Proarrhythmia results from the same mechanisms that cause other arrhythmias or from an alteration in the underlying substrate due to the antiarrhythmic agent. TdP is a rapid form of polymorphic VT associated with evidence of delayed ventricular repolarization due to blockade of potassium conductance. TdP may be hereditary or acquired. Acquired forms are associated with many clinical conditions and drugs, especially class Ia and class III IKr blockers.

Ventricular Fibrillation

• VF is electrical anarchy of the ventricle resulting in no cardiac output and cardiovascular collapse. Sudden cardiac death occurs most commonly in patients with coronary artery disease and those with LV dysfunction. VF associated with acute MI may be classified as either (1) primary (an uncomplicated MI not associated with HF) or (2) secondary or complicated (an MI complicated by HF).

BRADYARRHYTHMIAS

• Sinus bradyarrhythmias (heart rate <60 beats/min) are common, especially in young, athletically active individuals, and are usually asymptomatic and do not require intervention. However, some patients have sinus node dysfunction (sick sinus syndrome) because of underlying organic heart disease and the normal aging process, which attenuates SA nodal function. Sinus node dysfunction is usually representative of diffuse conduction disease, which may be accompanied by AV block and by paroxysmal tachycardias such as AF. Alternating bradyarrhythmias and tachyarrhythmias are

referred to as the tachy–brady syndrome.

• AV block or conduction delay may occur in any area of the AV conduction system. AV block may be found in patients without underlying heart disease (eg, trained athletes) or during sleep when vagal tone is high. It may be transient when the underlying etiology is reversible (eg, myocarditis, myocardial ischemia, after cardiovascular surgery, or during drug therapy). β-Blockers, digoxin, or nondihydropyridine calcium antagonists may cause AV block, primarily in the AV nodal area. Class I antiarrhythmics may exacerbate conduction delays below the level of the AV node. AV block may be irreversible if the cause is acute MI, rare degenerative diseases, primary myocardial disease, or congenital heart disease.

CLINICAL PRESENTATION

• Supraventricular tachycardias may cause clinical manifestations ranging from no symptoms to minor palpitations or irregular pulse to severe and even life-threatening symptoms. Patients may experience dizziness or acute syncopal episodes, symptoms of HF, anginal chest pain, or, more often, a choking or pressure sensation during the tachycardia episode.

• AF or atrial flutter may be manifested by the entire range of symptoms associated with other supraventricular tachycardias, but syncope is uncommon. Arterial embolization from atrial stasis and poorly adherent mural thrombi may result in embolic stroke.

• PVCs often cause no symptoms or only mild palpitations. The presentation of VT may vary from totally asymptomatic to pulseless hemodynamic collapse. Consequences of proarrhythmia range from no symptoms to worsening of symptoms to sudden death. VF results in hemodynamic collapse, syncope, and cardiac arrest.

• Patients with bradyarrhythmias experience symptoms associated with hypotension, such as dizziness, syncope, fatigue, and confusion. If LV dysfunction exists, patients may experience worsening HF symptoms.

DIAGNOSIS

• Electrocardiogram (ECG) is the cornerstone of diagnosis for cardiac rhythm disturbances.

• Cardiac auscultation can reveal the irregularly irregular pulse characteristic of AF.

• Proarrhythmia can be difficult to diagnose because of the variable nature of underlying arrhythmias.

• TdP is characterized by long QT intervals or prominent U waves on the surface ECG.

• Specific maneuvers may be required to delineate the etiology of syncope associated with bradyarrhythmias. Diagnosis of carotid sinus hypersensitivity can be confirmed by performing carotid sinus massage with ECG and blood pressure monitoring. Vasovagal syncope can be diagnosed using the upright body-tilt test.

• Based on ECG findings, AV block is usually categorized as first-, second-, or thirddegree AV block.

TREATMENT

• Goals of Treatment: The desired outcome depends on the underlying arrhythmia. For example, the goals of treating AF or atrial flutter are restoring sinus rhythm, preventing thromboembolic complications, and preventing further recurrences.

GENERAL APPROACH

• Use of antiarrhythmic drugs has declined because major trials showed increased mortality with use in several situations, the realization of proarrhythmia as a significant side effect, and the advancing technology of nondrug therapies, such as ablation and the implantable cardioverter-defibrillator (ICD).

CLASSIFICATION OF ANTIARRHYTHMIC DRUGS

• Drugs may depress the automatic properties of abnormal pacemaker cells by decreasing the slope of phase 4 depolarization and/or by elevating threshold potential. Drugs may alter conduction characteristics of the pathways of a reentrant loop.

• The Vaughan Williams classification is most frequently used (Table 6–1). Class Ia drugs slow conduction velocity, prolong refractoriness, and decrease the automatic properties of sodium-dependent (normal and diseased) conduction tissue. Class Ia drugs are effective for both supraventricular and ventricular arrhythmias.

• Although categorized separately, class Ib drugs probably act similarly to class Ia drugs, except that class Ib agents are considerably more effective in ventricular than supraventricular arrhythmias.

• Class Ic drugs slow conduction velocity while leaving refractoriness relatively unaltered. Although effective for both ventricular and supraventricular arrhythmias, their use for ventricular arrhythmias has been limited by the risk of proarrhythmia.

• Class I drugs are sodium channel blockers. Antiarrhythmic sodium channel receptor principles account for drug combinations that are additive (eg, quinidine and mexiletine) and antagonistic (eg, flecainide and lidocaine), as well as potential antidotes to excess sodium channel blockade (sodium bicarbonate).

• Class II drugs include β-adrenergic antagonists; effects result from antiadrenergic actions. β-Blockers are most useful in tachycardias in which nodal tissues are abnormally automatic or are a portion of a reentrant loop. These agents are also helpful in slowing ventricular response in atrial tachycardias (eg, AF) by effects on the AV node.

• Class III drugs prolong refractoriness in atrial and ventricular tissue and include very different drugs that share the common effect of delaying repolarization by blocking potassium channels.

✓ Amiodarone and sotalol are effective in most supraventricular and ventricular tachycardias. Amiodarone displays electrophysiologic characteristics consistent with each type of antiarrhythmic drug. It is a sodium channel blocker with relatively fast on-off kinetics, has nonselective β-blocking actions, blocks potassium channels, and has slight calcium-blocking activity. Sotalol inhibits outward potassium movement during repolarization and also possesses nonselective β-blocking actions. Dronedarone, ibutilide, and dofetilide are indicated only for treatment of supraventricular arrhythmias.

• Class IV drugs inhibit calcium entry into cells, which slows conduction, prolongs refractoriness, and decreases SA and AV nodal automaticity. Calcium channel antagonists are effective for automatic or reentrant tachycardias that arise from or use the SA or AV nodes.

ATRIAL FIBRILLATION OR ATRIAL FLUTTER

• Treatment of AF involves several sequential goals. First, evaluate need for acute treatment (usually with drugs that slow ventricular rate). Next, consider methods to restore sinus rhythm, considering risks involved (eg, thromboembolism). Lastly, consider ways to prevent long-term complications, such as recurrent arrhythmia and thromboembolism

• In patients with new-onset AF or atrial flutter with signs and/or symptoms of hemodynamic instability (eg, severe hypotension, angina, and/or pulmonary edema), direct-current cardioversion (DCC) is indicated to restore sinus rhythm immediately without regard to the risk of thromboembolism).

• If patients are hemodynamically stable, the focus should be directed toward controlling ventricular rate. Use drugs that slow conduction and increase refractoriness in the AV node as initial therapy. In patients with normal LV function (left ventricular ejection fraction [LVEF] >40%), IV β-blockers (propranolol, metoprolol, and esmolol), diltiazem, or verapamil are recommended as first-line therapy. If a high adrenergic state is the precipitating factor, IV β-blockers can be highly effective and should be considered first. In patients with LVEF less than or equal to 40%, avoid IV diltiazem and verapamil, and use IV β-blockers with caution. In patients having an exacerbation of HF symptoms, use IV digoxin or amiodarone as first-line therapy for ventricular rate control. IV amiodarone can also be used in patients who are refractory or have contraindications to β-blockers, nondihydropyridine calcium channel blockers, and digoxin.

• After treatment with AV nodal blocking agents and a subsequent decrease in ventricular response, assess the patient for the possibility of restoring sinus rhythm if AF persists.

• If sinus rhythm is to be restored, initiate anticoagulation prior to cardioversion because return of atrial contraction increases risk of thromboembolism. Patients become at increased risk of thrombus formation and a subsequent embolic event if the duration of AF exceeds 48 hours.

✓ Patients with AF for longer than 48 hours or an unknown duration should receive warfarin (target international normalized ratio [INR] 2.0–3.0), a low-molecularweight heparin (subcutaneously at treatment doses), or dabigatran for at least 3 weeks prior to cardioversion. If cardioversion is successful, continue anticoagulation with either warfarin or dabigatran for at least 4 weeks.

✓ Patients with AF less than 48 hours in duration do not require anticoagulation prior to cardioversion, but they should receive either IV unfractionated heparin or a low-molecular-weight heparin (subcutaneously at treatment doses) at presentation prior to and proceeding to cardioversion. If cardioversion is successful, continue anticoagulation with either warfarin or dabigatran for at least 4 weeks.

• After prior anticoagulation (or after transesophageal echocardiography demonstrated absence of a thrombus, obviating need for warfarin), methods for restoring sinus rhythm are pharmacologic cardioversion and DCC. DCC is quick and more often successful, but it requires prior sedation or anesthesia and has a small risk of serious complications, such as sinus arrest or ventricular arrhythmias. Advantages of initial drug therapy are that an effective agent may be determined in case long-term therapy is required. Disadvantages are significant side effects, such as drug-induced TdP, drug-drug interactions, and lower cardioversion rate for drugs compared with DCC. There is good evidence for efficacy of class III pure Ik blockers (ibutilide and dofetilide), class Ic drugs (eg, flecainide and propafenone), and amiodarone (oral or IV). With the “pill in the pocket” approach, outpatient, patientcontrolled self-administration of a single, oral loading dose of either flecainide or propafenone can be relatively safe and effective for termination of recent-onset AF in select patients without sinus or AV node dysfunction, bundle-branch block, QT interval prolongation, Brugada’s syndrome, or structural heart disease. It should only be considered for patients who have been successfully cardioverted with these drugs on an inpatient basis.

• Long-term antithrombotic therapy is recommended to prevent stroke. Patients with a CHADS2 (acronym derived from stroke risk factors: congestive heart failure, hypertension, age >75 years, diabetes, and prior stroke or transient ischemic attack) score of 2 or greater, 1, or 0 are considered to be at high risk, intermediate risk, and low risk for stroke, respectively. For patients at high or intermediate risk for stroke, oral anticoagulation is preferred over aspirin or aspirin plus clopidogrel; dabigatran antithrombotic therapy or aspirin is recommended; however, no therapy is preferred.

If the decision is made to initiate antithrombotic therapy in low-risk patients, aspirin 75–325 mg/day can be used.

• In patients with nonvalvular AF, warfarin, dabigatran, rivaroxaban, and apixaban are all indicated for prevention of initial and recurrent strokes.

✓ Dabigatran 150 mg twice daily is an effective alternative to warfarin for initial or recurrent stroke prevention in patients with at least one additional risk factor for stroke and a CrCl greater than 30 mL/min (>0.50 mL/s).

✓ Rivaroxaban 20 mg daily is an alternative to warfarin in patients at moderate-tohigh risk of stroke (eg, prior history of TIA, stroke or systemic embolism, or at least 2 additional risk factors for stroke).

✓ Apixaban 5 mg twice daily is an effective alternative to warfarin in patients with at least one risk factor for stroke. Apixaban is also an alternative to aspirin in patients with at least 1 risk factor for stroke and who are considered unsuitable candidates for warfarin.

• Dual antiplatelet therapy with aspirin plus clopidogrel is recommended over aspirin monotherapy for patients at high or intermediate risk for stroke who are not candidates for oral anticoagulation for reasons other than bleeding (ie, patient preference, unable to adhere to monitoring requirements).

• Consider chronic antithrombotic therapy for all patients with AF and risk factors for stroke regardless of whether or not they remain in sinus rhythm.

• AF often recurs after initial cardioversion because most patients have irreversible underlying heart or lung disease. A meta-analysis confirmed that quinidine maintained sinus rhythm better than placebo; however, 50% of patients had recurrent AF within 1 year, and quinidine increased mortality, presumably due in part to proarrhythmia.

Class Ic or III antiarrhythmic agents are reasonable alternatives to consider for maintaining sinus rhythm. Because the class Ic drugs flecainide and propafenone increase the risk of proarrhythmia, they should be avoided in patients with structural heart disease. Amiodarone is the most effective and most frequently used class III agent for preventing AF recurrences despite its potential for significant organ toxicity.

PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA

• The choice between pharmacologic and nonpharmacologic methods for treating PSVT depends on symptom severity (Fig. 6–2). Treatment measures are directed first at terminating the acute episode and then at preventing recurrences. For patients with severe symptoms (eg, syncope, near syncope, anginal chest pain, or severe HF), synchronized DCC is the treatment of choice. If symptoms are mild to moderate, nondrug measures that increase vagal tone to the AV node (eg, unilateral carotid sinus massage and Valsalva maneuver) can be used initially. If these methods fail, drug therapy is the next option.

• The choice among drugs is based on the QRS complex (see Fig. 6–2). Drugs can be divided into three broad categories: (1) those that directly or indirectly increase vagal tone to the AV node (eg, digoxin); (2) those that depress conduction through slow, calcium-dependent tissue (eg, adenosine, β-blockers, and nondihydropyridine calcium channel blockers); and (3) those that depress conduction through fast, sodiumdependent tissue (eg, quinidine, procainamide, disopyramide, and flecainide).

• Adenosine has been recommended as the drug of first choice for patients with PSVT because its short duration of action will not cause prolonged hemodynamic compromise in patients with wide QRS complexes who actually have VT rather than PSVT.

• After acute PSVT is terminated, long-term prophylaxis is indicated if frequent episodes necessitate therapeutic intervention or if episodes are infrequent but severely symptomatic. Serial testing of antiarrhythmic agents can be performed via ambulatory ECG recordings (Holter monitors) or telephonic transmissions of cardiac rhythm (event monitors) or by invasive electrophysiologic techniques in the laboratory.

• Consider transcutaneous catheter ablation using radiofrequency current on the PSVT substrate in any patient who would have previously been considered for chronic antiarrhythmic drug treatment. It is highly effective and curative, rarely results in complications, obviates need for chronic antiarrhythmic drug therapy, and is cost effective.

PREMATURE VENTRICULAR COMPLEXES

• In apparently healthy individuals, drug therapy is unnecessary because PVCs without associated heart disease carry little or no risk. In patients with risk factors for arrhythmic death (recent MI, LV dysfunction, or complex PVCs), limit chronic therapy to β-blockers because only they have been proven to prevent mortality in these patients.

VENTRICULAR TACHYCARDIA

Acute Ventricular Tachycardia

• If severe symptoms are present, institute synchronized DCC immediately to restore sinus rhythm and correct precipitating factors if possible. If VT is an isolated electrical event associated with a transient initiating factor (eg, acute myocardial ischemia or digitalis toxicity), there is no need for long-term antiarrhythmic therapy after precipitating factors are corrected.

• Patients with mild or no symptoms can be treated initially with antiarrhythmic drugs. IV procainamide, amiodarone, or sotalol may be considered in this situation; lidocaine is an alternative agent. Deliver synchronized DCC if the patient’s status deteriorates, VT degenerates to VF, or drug therapy fails.

Sustained Ventricular Tachycardia

• Patients with chronic recurrent sustained VT are at high risk for death; trial-anderror attempts to find effective therapy are unwarranted. Neither electrophysiologic studies nor serial Holter monitoring with drug testing is ideal. These findings and the side effect profiles of antiarrhythmic agents have led to nondrug approaches.

• The automatic ICD is a highly effective method for preventing sudden death due to recurrent VT or VF.

Ventricular Proarrhythmia

• The typical form of proarrhythmia caused by the class Ic antiarrhythmic drugs is a rapid, sustained, monomorphic VT with a characteristic sinusoidal QRS pattern that is often resistant to resuscitation with cardioversion or overdrive pacing. IV lidocaine (competes for the sodium channel receptor) or sodium bicarbonate (reverses the excessive sodium channel blockade) have been used successfully by some clinicians.

Torsade de Pointes

• For an acute episode of torsade de pointes (TdP), most patients require and respond to DCC. However, TdP tends to be paroxysmal and often recurs rapidly after DCC.

• IV magnesium sulfate is the drug of choice for preventing recurrences of TdP. If ineffective, institute strategies to increase heart rate and shorten ventricular repolarizatio (ie, temporary transvenous pacing at 105–120 beats/min or pharmacologic pacing with isoproterenol or epinephrine infusion). Discontinue agents that prolong the QT interval and correct exacerbating factors (eg, hypokalemia and hypomagnesemia). Drugs that further prolong repolarization (eg, IV procainamide) are contraindicated. Lidocaine is usually ineffective.

Ventricular Fibrillation

• Manage patients with pulseless VT or VF (with or without associated myocardial ischemia) according to American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care (see Chap. 7).

BRADYARRHYTHMIAS

• Treatment of sinus node dysfunction involves elimination of symptomatic bradycardia and possibly managing alternating tachycardias such as AF. Asymptomatic sinus bradyarrhythmias usually do not require therapeutic intervention.

• In general, a permanent ventricular pacemaker is the long-term therapy of choice for patients with significant symptoms.

• Drugs commonly employed to treat supraventricular tachycardias should be used with caution, if at all, in the absence of a functioning pacemaker.

• Symptomatic carotid sinus hypersensitivity also should be treated with permanent pacemaker therapy. Patients who remain symptomatic may benefit from adding an α-adrenergic stimulant such as midodrine.

• Vasovagal syncope has traditionally been treated successfully with oral β-blockers (eg, metoprolol) to inhibit the sympathetic surge that causes forceful ventricular contraction and precedes the onset of hypotension and bradycardia. Other drugs that have been used successfully (with or without β-blockers) include fludrocortisone anticholinergics (scopolamine patches and disopyramide), α-adrenergic agonists (midodrine), adenosine analogues (theophylline and dipyridamole), and selective serotonin reuptake inhibitors (sertraline and paroxetine).

Atrioventricular Block

• If patients with Mobitz II or third-degree AV block develop signs or symptoms of poor perfusion (eg, altered mental status, chest pain, hypotension, and/or shock) administer atropine (0.5 mg IV given every 3–5 minutes, up to 3 mg total dose). Transcutaneous pacing can be initiated in patients unresponsive to atropine. Infusions of epinephrine (2–10 mcg/min) or dopamine (2–10 mcg/kg/min) can also be used in the event of atropine failure. These agents usually do not help if the site of the AV block is below the AV node (Mobitz II or trifascicular AV block).

• Chronic symptomatic AV block warrants insertion of a permanent pacemaker. Patients without symptoms can sometimes be followed closely without the need for a pacemaker.

EVALUATION OF THERAPEUTIC OUTCOMES

• The most important monitoring parameters include:

 (1) mortality (total and due to arrhythmic death),

(2) arrhythmia recurrence (duration, frequency, and symptoms),

(3) hemodynamic consequences (rate, blood pressure, and symptoms), and

(4) treatment complications (side effects or need for alternative or additional drugs, devices,

or surgery).